Stepwise Differentiation of Human Adipose-Derived Mesenchymal Stem Cells Toward Definitive Endoderm and Pancreatic Progenitor Cells by Mimicking Pancreatic Development In Vivo

2013 ◽  
Vol 22 (10) ◽  
pp. 1576-1587 ◽  
Author(s):  
Jing Li ◽  
Li Zhu ◽  
Xuebin Qu ◽  
Jing Li ◽  
Ruizhu Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Definitive Endoderm ◽  
Pancreatic Development ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells

scholarly journals Human Fetal Bone Marrow-Derived Mesenchymal Stem Cells Promote the Proliferation and Differentiation of Pancreatic Progenitor Cells and the Engraftment Function of Islet-Like Cell Clusters

2019 ◽  
Vol 20 (17) ◽  
pp. 4083
Author(s):  
Xing Yu Li ◽  
Shang Ying Wu ◽  
Po Sing Leung
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Progenitor Cells ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
Proliferation And Differentiation ◽  
Differentiation And Proliferation

Pancreatic progenitor cells (PPCs) are the primary source for all pancreatic cells, including beta-cells, and thus the proliferation and differentiation of PPCs into islet-like cell clusters (ICCs) opens an avenue to providing transplantable islets for diabetic patients. Meanwhile, mesenchymal stem cells (MSCs) can enhance the development and function of different cell types of interest, but their role on PPCs remains unknown. We aimed to explore the mechanism-of-action whereby MSCs induce the in vitro and in vivo PPC/ICC development by means of our established co-culture system of human PPCs with human fetal bone marrow-derived MSCs. We examined the effect of MSC-conditioned medium on PPC proliferation and survival. Meanwhile, we studied the effect of MSC co-culture enhanced PPC/ICC function in vitro and in vivo co-/transplantation. Furthermore, we identified IGF1 as a critical factor responsible for the MSC effects on PPC differentiation and proliferation via IGF1-PI3K/Akt and IGF1-MEK/ERK1/2, respectively. In conclusion, our data indicate that MSCs stimulated the differentiation and proliferation of human PPCs via IGF1 signaling, and more importantly, promoted the in vivo engraftment function of ICCs. Taken together, our protocol may provide a mechanism-driven basis for the proliferation and differentiation of PPCs into clinically transplantable islets.

scholarly journals Genetic Modification of Primate Amniotic Fluid-Derived Stem Cells Produces Pancreatic Progenitor Cells in vitro

2013 ◽  
Vol 197 (4) ◽  
pp. 269-282 ◽  
Author(s):  
Yu Zhou ◽  
David L. Mack ◽  
J. Koudy Williams ◽  
Sayed-Hadi Mirmalek-Sani ◽  
Emily Moorefield ◽  
...  
Keyword(s):  
Stem Cells ◽  
Amniotic Fluid ◽  
Progenitor Cells ◽  
Genetic Modification ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells

scholarly journals Neurogenin3 inhibits proliferation in endocrine progenitors by inducing Cdkn1a

2010 ◽  
Vol 108 (1) ◽  
pp. 185-190 ◽  
Author(s):  
Takeshi Miyatsuka ◽  
Yasuhiro Kosaka ◽  
Hail Kim ◽  
Michael S. German
Keyword(s):  
Cell Cycle ◽  
Progenitor Cells ◽  
Kinase Inhibitor ◽  
Islet Cells ◽  
Cell Cycle Control ◽  
Final Size ◽  
Transgenic Expression ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells

During organogenesis, the final size of mature cell populations depends on their rates of differentiation and expansion. Because transient expression of Neurogenin3 (Neurog3) in progenitor cells in the developing pancreas initiates their differentiation to mature islet cells, we examined the role of Neurog3 in cell cycle control during this process. We found that mitotically active pancreatic progenitor cells in mouse embryos exited the cell cycle after the initiation of Neurog3 expression. Transcriptome analysis demonstrated that the Neurog3-expressing cells dramatically up-regulated the mRNA encoding cyclin-dependent kinase inhibitor 1a (Cdkn1a). In Neurog3 null mice, the islet progenitor cells failed to activate Cdkn1a expression and continued to proliferate, showing that their exit from the cell cycle requires Neurog3. Furthermore, induced transgenic expression of Neurog3 in mouse β-cells in vivo markedly decreased their proliferation, increased Cdkn1a levels, and eventually caused profound hyperglycemia. In contrast, in Cdkn1a null mice, proliferation was incompletely suppressed in the Neurog3-expressing cells. These studies reveal a crucial role for Neurog3 in regulating the cell cycle during the differentiation of islet cells and demonstrate that the subsequent down-regulation of Neurog3 allows the mature islet cell population to expand.

scholarly journals Isolation of Pancreatic Progenitor Cells with the Surface Marker of Hematopoietic Stem Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Fengxia Ma ◽  
Fang Chen ◽  
Ying Chi ◽  
Shaoguang Yang ◽  
Shihong Lu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Progenitor Cells ◽  
Culture System ◽  
Isolated Cells ◽  
Pancreatic Cell ◽  
Hematopoietic Stem ◽  
Pancreatic Progenitor ◽  
Pancreatic Progenitor Cells ◽  
Embryonic Pancreas

To isolate pancreatic progenitor cells with the surface markers of hematopoietic stem cells, the expression of stem cell antigen (Sca-1) and c-Kit and the coexpression of them with pancreatic duodenal homeobox-1 (PDX-1), neurogenin 3 (Ngn3), and insulin were examined in murine embryonic pancreas. Then different pancreatic cell subpopulations were isolated by magnet-activated cell sorting. Isolated cells were cultured overnight in hanging drops. When cells formed spheres, they were laid on floating filters at the air/medium interface. With this new culture system, pancreatic progenitor cells were induced to differentiate to endocrine and exocrine cells. It was shown that c-Kit and Sca-1 were expressed differently in embryonic pancreas at 12.5, 15.5, and 17.5 days of gestation. The expression of c-Kit and Sca-1 was the highest at 15.5 days of gestation. c-Kit rather than Sca-1 coexpressed with PDX-1, Ngn3, and insulin. Cells differentiated from c-Kit-positive cells contained more insulin-producing cells and secreted more insulin in response to glucose stimulation than that from c-Kit-negative cells. These results suggested that c-Kit could be used to isolate pancreatic progenitor cells and our new culture system permitted pancreatic progenitor cells to differentiate to mature endocrine cells.

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